Investigation of the Antiproliferative and Anticancer Effects of Calcitriol in KRAS mutant HCT-116 and Wild-type HT-29 Colorectal Cancer Cell Lines
Project no. 32533 · Status: Kapanmış · 2024
Summary
<p>Colorectal cancer is a type of cancer with high morbidity and mortality, and 50% of patients die within 5 years of diagnosis due to metastatic disease. The chemotherapy process negatively affects the physical and mental health of patients. Therefore, completing the chemotherapy process as quickly, effectively, and with as few side effects as possible should be one of the priorities in cancer treatment. Consequently, chemotherapy-supportive treatments with minimal side effects could be an alternative. The interaction between the KRAS protein and the Epidermal Growth Factor (EGF) receptor is a critical step in colorectal cancer initiation and progression. Due to KRAS mutations, observed in 40-50% of colorectal cancer cases, EGFR-targeted therapies such as panitumumab and cetuximab are ineffective.</p><p>Studies conducted on liver cancer have found that increased calcium levels - whose uptake can be modified by altering the number of calcium channel proteins in the cell membrane - reduce EGFR transcription in KRAS mutant cells. Based on this, it is hypothesized that a similar effect might be observed in KRAS mutant colorectal cancer cells. Calcitriol, the active form of Vitamin D, is known to increase the number of calcium channel proteins in gastrointestinal tract cells, and calcitriol has been reported to demonstrate antiproliferative effects in many cancer types in other studies. A study investigating the effect of calcitriol in a KRAS wild-type colorectal cancer cell line has been reported. However, inspired by the study performed in liver cancer, a comparative study investigating whether calcitriol's antiproliferative effect in KRAS mutant colorectal cancer cells is mediated by altering EGFR levels, as suggested by the liver cancer study, has not been encountered. To address this, KRAS mutant and wild-type HT-29 and HCT-116 colorectal cancer cell lines will be used. In wild-type and mutant KRAS cell lines, the expression levels of critical genes in the EGF and KRAS signaling pathways will be measured following calcitriol treatment. The aim of the project is to demonstrate the inhibition of the KRAS signaling pathway by calcitriol treatment in the KRAS mutant cell line. If such a result is achieved, it is thought that calcitriol could offer a therapeutic option in mutant KRAS tumors where EGFR inhibitors are ineffective, and that a significant contribution will be made to the literature.</p>